In Episode #75, Dr. Jill interviews Dr. Dale Bredesen and discusses his new book, The First Survivors of Alzheimer's. The Bredesen protocol shows us how to rebalance using lifestyle modifications like taking B12, eliminating gluten, or improving oral hygiene, treating infections and metabolic syndrome.
Key Points
- We discuss 36 metabolic factors (micronutrients, hormone levels, and sleep) that can trigger “downsizing” in the brain.
- The Bredesen protocol shows us how to rebalance these factors using lifestyle modifications like taking B12, eliminating gluten, or improving oral hygiene, treating infections or metabolic syndrome.
- We review the subtypes of Alzheimer’s disease: (1) Inflammatory (hot) includes those with the ApoE4 genotypes, (2) Atrophic (cold), and (3) Toxic (exposure to chemicals and infections). These types are clarified by the testing, and some patients, especially those with ApoE4 genotypes, have a combination of types 1 and 2 (4) Vascular and (5) Traumatic
Guest – Dr. Dale Bredesen
Dale Bredesen, M.D., is internationally recognized as an expert in the mechanisms of neurodegenerative diseases such as Alzheimer's disease, and the author of the New York Times bestsellers The End of Alzheimer's (Avery, 2017) and The End of Alzheimer's Program (Avery, 2020). He has held faculty positions at UC San Francisco, UCLA, and the University of California San Diego, and directed the Program on Aging at the Burnham Institute before coming to the Buck Institute for Research on Aging in 1998 as its founding president and CEO. He is currently a professor at UCLA.
https://www.apollohealthco.com/dr-bredesen/
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Dr. Jill
Dr. Jill Carnahan is Your Functional Medicine Expert® dually board certified in Family Medicine for ten years and in Integrative Holistic Medicine since 2015. She is the Medical Director of Flatiron Functional Medicine, a widely sought-after practice with a broad range of clinical services including functional medical protocols, nutritional consultations, chiropractic therapy, naturopathic medicine, acupuncture, and massage therapy. As a survivor of breast cancer, Crohn’s disease, and toxic mold illness she brings a unique perspective to treating patients in the midst of complex and chronic illness. Her clinic specializes in searching for the underlying triggers that contribute to illness through cutting-edge lab testing and tailoring the intervention to specific needs.
Featured in Shape Magazine, Parade, Forbes, MindBodyGreen, First for Women, Townsend Newsletter, and The Huffington Post as well as seen on NBC News and Health segments with Joan Lunden, Dr. Jill is a media must-have. Her YouTube channel and podcast features live interviews with the healthcare world’s most respected names.
A popular inspirational speaker and prolific writer, she shares her knowledge of hope, health, and healing live on stage and through newsletters, articles, books, and social media posts! People relate to Dr. Jill’s science-backed opinions delivered with authenticity, love and humor. She is known for inspiring her audience to thrive even in the midst of difficulties.
The Podcast
The Video
The Transcript
#75: Dr. Jill Interviews Dr. Dale Bredeson on Reversal of Alzheimer's Disease
Dr. Jill 00:12
Hello everyone! We are live—just checking, it looks like we're on—and I am so excited about my guest today. We met maybe five or six years ago and I'm so excited to introduce his new book and the work that Dr. Dale Bredesen is doing to change the landscape of Alzheimer's and dementia. I am super excited to introduce him.
Dr. Jill 00:36
Before I introduce him, just a little housekeeping bit: You can find any information on blogs or things I've written at JillCarnahan.com. We're now live on both YouTube and iTunes and anywhere you find podcasts. You can hear this and all of those and listen at your leisure and it'll be posted there in the next several days. Like I said, there are lots and lots of other interviews available and lots of free blogs and writings there.
Dr. Jill 01:02
Let me introduce my guest, Dr. Dale Bredesen. Dr. Dale Bredesen is internationally recognized as an expert in the mechanisms of neurodegenerative diseases such as Alzheimer's and the author of a New York Times best-selling book, The End of Alzheimer's, from Avery in 2017. He also authored The End of Alzheimer's Program in 2020. He has held faculty positions at UC San Francisco, UCLA, and the University of California, San Diego, and directed the program on aging at the Burnham Institute before coming to the Buck Institute for Research on Aging in 1998 as its founding president and CEO. He's currently a professor at UCLA. I think that's where I met you at the Buck Institute with one of your first events, probably like I said five or six years ago. Just fascinating—your research. I remember the inhalation Alzheimer's article; what was the title? What was the title of that published article that you had?
Dr. Dale Bredeson 01:58
Yes, “Inhalational Alzheimer's disease: an unrecognized—and treatable—epidemic”. The idea was basically what you've been seeing: So many people have cognitive effects from being exposed to mycotoxins. We're seeing so many people who have Alzheimer's by all the criteria—PET scans, spinal fluid, etc.—and of the many contributors, often the dominant one is mycotoxins.
Dr. Jill 02:26
Yes. And that's my world. I see the same thing. I don't consider myself an expert in Alzheimer's, but based on your research, I've certainly learned a lot. And I remember something you said—and correct me if this has changed—at one point in some of your research groups, which we'll talk about today, you said that especially the younger patients presenting with Alzheimer's, there was about one in three that had some mycotoxin exposure. Does that still somewhat hold true?
Dr. Dale Bredeson 02:52
Yes. If anything, it may have gone up some. When I was training way back in the '80s, we never saw people who were in their 40s and 50s with Alzheimer's disease. This was in the late '60s, '70s, and '80s. But the epidemiology has shown that there are many more young Alzheimer's [patients] these days. That has increased. When we look at those people, they're often in their late 40s or early 50s, often around the time of menopause or andropause. These are people who often present differently.
Dr. Dale Bredeson 03:25
They often have some degree of depression. They often have a non-amnestic presentation—not always, but that's a common thing—and they have executive problems. They will often lose their jobs because they can't plan anymore and they can't execute anymore. They'll often have some dyscalculia. They sometimes have posterior cerebral atrophy, so-called PCA or PPA, or primary progressive aphasia—word-finding issues. It's more of a biparietal than it is a classical bitemporal, where you lose memory. There's often a different presentation. And these people usually turn out to have some form of toxicity. The most common one is mycotoxicity. This hadn't been recognized by the Alzheimer's community, so I think it's important for all of us to keep that in mind, as you know better than anyone. You're a real-world expert in this area.
Dr. Jill 04:21
Thank you, Dr. Bredesen. And I have the greatest respect for the work you're doing because it is giving us solutions to something that we thought was previously unsolvable. We just assumed these people had to put their affairs in order, and we don't see that as much anymore, especially when we catch it early. I love seeing these people who are younger with a toxic load because I feel like I can make the most change in them.
Dr. Jill 04:44
Let's go back. I want to talk about your first work. And give a groundwork for the holes in the roof and the theory of Alzheimer's. But before I do, I want to hear your story: How did you get interested in this area of study? And what was your journey to get to the Buck Institute? Tell us just a little about how you got there.
Dr. Dale Bredeson 05:01
Yes, thanks. I was very interested in neurodegenerative disease. I was a postdoctoral fellow in Dr. Stan Prusiner's lab before he won the Nobel Prize in 1997. I wanted to set up my own lab to understand what drives the neurodegenerative process. We wanted to understand the molecular details. Why is it that it's very common? Why is it that it's completely untreatable? As you know, the area of neurodegenerative disease has been the area of greatest biomedical therapeutic failure. Whether you have frontotemporal dementia, Lewy body [dementia], Alzheimer's, or ALS, we just tell you we're very sorry. We wanted to understand why that is, and we spent years doing this. I went to the Buck [Institute] from San Diego because, at the time, they were just going to open this new research institute on aging and I had this wonderful opportunity to be the founding president and CEO. I thought, “Okay, let's begin to understand this underlying process.”
Dr. Dale Bredeson 05:56
The surprise was that when we looked at it, it's quite different from the usual claim about Alzheimer's, which is that it's some sort of misfolded protein and the problem in the brain is that your proteins aren't folding correctly. Well, sure—as part of a much larger problem. But what we found is that if you go to the heart of what Alzheimer's is, it is an insufficiency. On the positive side, you've got things that are supporting you, like your hormones, your trophic factors and your nutrients, your energetics, your mitochondrial function, blood flow, and oxygenation. On the negative side, you've got the demands, and those are things like pathogens, toxins, or anything that is creating more demand on the system.
Dr. Dale Bredeson 06:44
When we're young, we balance those pretty nicely. And this dwarfs the COVID-19 pandemic, unfortunately: We're looking at over 600,000 [people] who've been killed by COVID-19, but about 45 million currently living Americans are destined to die of Alzheimer's if we don't find something that's really helpful. It's a huge pandemic. When you look at that, you see this balance and you see that everybody with Alzheimer's is on the wrong side of that balance.
Dr. Dale Bredeson 07:16
You can trace the molecular pathway. The amyloid precursor protein itself sits in your neuronal membranes. And when things are bad, it essentially goes into a protective downsizing mode. It's interesting because it's an analogy to what's happened to our country with COVID-19. We were all told about a year and a half ago to shelter in place and social distance. The country went into a recession—a protective downsizing mode. Your brain does the same thing through APP processing when you have a supply that's not meeting the demand, so you involute.
Dr. Dale Bredeson 07:52
We realize that this is a very different model. Instead of just trying to get rid of amyloid, we need to look for each person. As we started going through, we initially identified 36 different contributors. The good news is that it's not thousands, but it's dozens, so we said to the patients: “Imagine you have a roof with 36 holes in it. A drug is an excellent way to patch one hole, but you've got to do the other ones.” I think in the long run, drugs and these precision functional medicine protocols are going to work together to do this.
Dr. Dale Bredeson 08:27
But the surprise was just what you're studying. The surprise was that, as we looked at these people, we saw that there was a whole group where mycotoxins were the critical players in this downsizing event. It was surprising because it hadn't been in the literature. As you said, when you see these people, you have to get on and treat their mycotoxicity. And often they also have things like insulin resistance, sleep apnea, changes in their oral or gut microbiome, leaky gut, and on and on and on. Unlike this idea [where] you just write a prescription for one thing and you're going to cover all 36 holes with one little hunk of paper—that just doesn't work—you have to take a more functional medicine approach just as you do.
Dr. Jill 09:13
Yes. Gosh, I love that. I love that I was trained as a medical doctor, an allopathic MD. We had great training just like you, and we have these wonderful toolboxes. I think drugs are absolutely appropriate. But what happens is that with this personalized functional medicine approach, we're going to the root cause and we've got a bigger toolbox. The exciting thing is that now we have things that we didn't have before. [With] some of the nutritional stuff, I wasn't trained in medical school. I had to learn post-graduately: What does zinc do in these pathways? What does magnesium do? Even with the hormonal stuff, we learned it all in the second year. Then we have to go back and relearn those metabolic pathways in depth, because they matter.
Dr. Jill 09:52
I love that you touched on amyloid plaques and some of the anti-amyloid drugs. Do you want to talk a little bit about that? I want people to understand how that's protective. And when we started to attack, we saw that these drugs didn't work like we thought. Do you want to talk a little bit about amyloid and what its purpose is?
Dr. Dale Bredeson 10:08
Absolutely. That's one of the big surprises. This was supposed to be the villain that was causing the disease. But it turns out it's a response to multiple different pathogens. It turns out to be an antimicrobial peptide, for example. In fact, your body is making this because you've got these various insults. And the pathologists have already shown us. You look in the brains of patients with Alzheimer's, you see P. gingivalis from poor dentition, you see herpes simplex from the lip, you see molds from things like chronic sinusitis, and you see spirochetes, and on and on. This stuff is making this to cover this. So you've got to think in a different way. Instead of just getting rid of the amyloid, which is what these drugs do, you have to look at what's causing the amyloid and address those things.
Dr. Dale Bredeson 10:08
As you indicated, back on June 7th, the FDA took a very unusual step. They approved a drug, Aduhelm, which is aducanumab, that all 11 out of the 11 experts on their panel said should not be approved. Ten of them strongly recommended against it. One of them said, “I don't know.” Nobody said this should be approved. And they thought: If you want to approve it, do another trial because one trial failed completely. One trial had a minimal benefit in that it didn't make you better, but it made things go downhill slightly less quickly—22%. But at the risk of: 17% of the people developed microhemorrhages within the brain, and 40% of them developed brain swelling.
Dr. Dale Bredeson 11:44
Some people have described this as the gaffe that keeps on giving because it was an unusual, unusual decision. In fact, three of the people from the board then resigned in protest. Now there's a congressional inquest into what the heck happened. Why was this approved? Not only does it not help you much and have side effects, but it costs about $100,000 per year—$56,000 for the drug.
Dr. Jill 12:08
Wow!
Dr. Dale Bredeson 12:10
I know. It's really bizarre. And then, of course, more for the infusions and all the scans you have to get, so you're looking at about $100,000 per year. Taking a functional medicine approach is far, far more effective and far, far cheaper, getting much, much better outcomes.
Dr. Jill 12:29
Yes. This is so important. If we had drugs that worked, there's nothing wrong with that. But what we're seeing is that they're not addressing the root cause at this moment. As we look, even your research, I think, is driving a better thought process around what might help.
Dr. Jill 12:46
Do you want to frame your first book? You talked about the different classes for people who aren't familiar with that. First of all, the name of your first book—repeat that for our listeners. And where can they find your books?—because I think this is really important.
Dr. Dale Bredeson 12:59
The first book was called The End of Alzheimer's. To be fair, that was a name that came from Random House, not from me.
Dr. Jill 13:07
I get it.
Dr. Dale Bredesen 13:08
My name for the book was ‘Wits End,' which was suggested by my wife because that's both the research and the disease. I thought that was a wonderful idea. Random House said, “Nobody will ever buy a book called ‘Wits End', so we're going to call it ‘The End of Alzheimer's.'” We've gotten a little pushback on that. But the point was simply to say that for the first time, we're beginning to understand what this process is. It was about the science and “Here are some people who've gotten better.”
Dr. Dale Bredesen 13:33
Recently, we finally got to the point of doing a clinical trial, which is now posted on medRxiv. After the first book, everybody said, “We want more details!” So then the second book was about details. The third book that just came out is all about the survivors talking about their stories and what they went through. As you indicated, one of the parts of the first book was to say that when you start to look at all these different players—you're looking at inflammation, and you're looking at the microbiome and all these things—what you find is that Alzheimer's is not one disease. It's really six different subtypes. There are people who are more on the inflammatory side. There are people who are more on the atrophic side.
Dr. Dale Bredesen 14:13
There's an interesting mix of those people who are glycotoxic and have the insulin resistance that gives them type 2, the atrophic [kind], but they also have the glycotoxicity. They have non-enzymatic glycation of hundreds of proteins, which we measure as hemoglobin A1c, but there are many others affected. They've got the worst of both worlds—a very common problem. That's type 1.5. Type 3 is toxins. There are three different ones. [One is] the inorganics, including for all of us who've been in the Western fires, we are at increased risk. No question, air pollution increases your risk. And then the organics—things like glyphosate, toluene, and benzene and things like that. And then there are the biotoxins, things like trichothecenes, and all the things that you're dealing with on a daily basis. That's type 3. Type 4 is vascular. Type 5 is traumatic.
Dr. Dale Bredesen 15:04
Different people have different presentations. As you said, you have to get to the root cause for each person. You have to have a personalized, precision medicine-type approach to get the best outcomes. We're seeing better and better outcomes in the trial that we just completed. I was really honored to work with Dr. Anne Hathaway, Dr. Kat Toups, and Dr. Deborah Gordon. They were just fantastic. And of course, they sing your praises as well. They did a great job. And 84% of the people improved—they didn't just slow their decline but improved their scores. The most exciting part is that we now have people who are over nine years with sustained improvement, which was unheard of before, so we're very excited. Nevertheless, there are a few people who don't, and we'd like to understand why. What is being missed? Are they too far along? If they are far along, are there things that we need to be adding? What is missing so that we can help every single person? The good news is that if you start early, just about everybody gets better.
Dr. Dale Bredesen 16:05
The reality is that Alzheimer's is becoming an option. Nobody has to get this. If you simply get on prevention or early reversal, you have quite a window. SCI itself, or subjective cognitive impairment, lasts, on average, 10 years. And that's a very early stage. The big concern is something called mild cognitive impairment. As one of the seven survivors wrote, Frank, when his doctor first told him he had MCI, he said, “There's nothing mild about this.” That's the problem. It's the third of four stages. It's not the pre-symptomatic. It's not the SCI, but it's the third stage out of four. It's a little bit like telling someone: “Oh, don't worry; you've got mildly metastatic cancer.” This is a relatively late stage, so you want to get into everything possible. But preferably, you never get to that stage.
Dr. Jill 16:59
I love this, Dr. Bredesen. My patient population isn't like a brain clinic or an Alzheimer's clinic. But what I see are people in their 20s, 30s, and 40s—young, young people. So if you're listening and you're starting to have cognitive impairment of any type, this is not normal. Find a doctor who can help you find the root cause, because if we get awareness—people in their 20s, 30s, and 40s—we could probably make even a bigger change because that's where you have complete plasticity to make a difference and to see your toxic load and your metabolic status. I always think of health as a trajectory and we're either walking towards disease or away from it. If you're proactive as a younger person, you can change this. You can find your ApoE4 status to see if you have that or not, because that's going to put you at higher risk, meaning you need to start earlier for prevention.
Dr. Jill 17:49
I wanted to mention your type 3s. That's primarily part of my practice. I had an incident—just three of those things in my personal brain health. Recently, we had the fires. If you look, I've got an article coming out this week on all the toxic metals, chemicals, benzenes, and things that are in this fire/smoke. We're seeing—Dr. Ackerland and I just talked—that TGF-β, which is an inflammatory marker in the blood, will go up just from the smoke and fires. Some of these things are affecting markers in the blood. And I had that incident with my breathing.
Dr. Jill 18:20
Then my car was in a little accident—a fender bender, a minor thing—but it had to be painted. I got it back from the auto body shop and for two days, I was narcoleptic. I'd get out of that car after 30 minutes, but the VOCs from that toxic auto body paint, the benzenes, and those chemicals put me comatose for almost two days. I thought it was worse than a mold exposure. For people who are in that industry, if you're not aware, those things are so toxic to the brain. And then I pulled up the studies and there are lawsuits out for people who've been in paint and body shops for auto body types of things because it's so toxic—the benzenes and stuff. We had the smoke from the fires, and I had all these experiences.
Dr. Jill 18:59
Then recently, I had a friend who had Chaetomium in the house and I had an exposure there. And the same thing: For a whole 24 hours, I could not think or function. This is very real. I'm in my 40s. And I have really good cognitive [function]; I don't feel like I have an impairment. But even so, just those exposures in one day take me out. It makes it really difficult to process. So we need to be thinking about how we can have good air quality and how we can prevent it because, like you said, you're getting these people and you're making reversals when they're diagnosed. And then, for people like me, my job is to find the pre-clinical states. And, how do we keep people from ever walking toward that disease?
Dr. Dale Bredeson 19:38
And we should. That's the thing. This disease should be very rare. It's because people don't realize that. And we're all told there's nothing you can do and they wait too long. And you've brought up a critical issue, which is brain fog. This is something that affects so many people. And with COVID-19, it's becoming even more important. There's a big concern that in the future, we'll have a huge increase in Alzheimer's disease because of all these people who've gotten COVID-19 and have had some brain fog got better, but are now at risk for decline. There's no question that this virus does affect the brain. It does infect the vessels within the brain, for example. It's got neuroinflammation as part of it. It really does, by multiple mechanisms, increase your risk. And there've already been a few patients with Parkinson's. That came on literally with COVID-19, so there is a concern that there will be neurotropic-related effects of this virus down the road.
Dr. Dale Bredeson 20:36
Therefore, we always recommend to anyone who's had this to please get on prevention. Please get what we call a cognoscopy. Everyone knows you should get a colonoscopy when you turn 50. We all recommend to everyone who's 45 or over to please get a cognoscopy. It's actually much more pleasant than a colonoscopy. You can find out where you stand and see the sort of things you were just talking about: Have you had exposure to these various things?—because they will indeed increase your risk.
Dr. Jill 21:04
I love this. You're training doctors. I have a limited practice. But there are doctors out there—the ones you mentioned that you're doing research with—some good friends of both of ours who are doing this. How do people find your work and the doctors who've been trained with the recode? Tell us just a little about—for those people listening—how do they find a good doctor that does what you have been teaching?
Dr. Dale Bredeson 21:25
Yes, that's a great point. You can just go on DrBredesen.com or you can go on ApolloHealthCo.com. We're working with Apollo Health because we believe that the future of medicine is in larger datasets. It's so interesting to me; Google knows where you shop. Google knows a lot about your life. They're gathering all this data. Yet why is it that we as physicians aren't gathering it in these incredibly complicated people that we're dealing with, human organisms? We should be looking at much, much larger datasets. But the way you and I were trained—especially way back in the caveman era when I was training because I'm much older—back then people would basically say, “What's the disease?” and make a diagnosis, write a prescription, or send them to surgery. And there was no asking why. There was no understanding of physiological changes. If someone had hypertension, you wrote a prescription for antihypertensives instead of asking, “Why did they get hypertension?” I think this is part of 21st-century medicine.
Dr. Jill 22:25
I love it. Years ago, I was the outcast in medical school who did an integrative club. I brought in different modalities and exposure [to it] at Loyola. I was one of the first who was really talking about it in medical school. But what's interesting—people thought I was a little crazy back then—now my colleagues call me all the time and say, “Jill, I have this problem I can't solve. Do you have any… ” We went into medicine wanting to heal people. And if our hearts are in that healing space, when we encounter things that we don't have answers to, we say why? Is there anything else? So that's why you, me, and all of our colleagues who are doing this are open to other things.
Dr. Jill 23:01
My thing is always risk-benefit analysis. If there's something like adding extra vitamin C or checking hormone status and the risk is very low with an intervention, even if I don't know for sure that there's a very large randomized controlled trial out there to prove it, I will often try things that I feel like are incredibly safe because the risk is very low. And that's how I usually determine what kinds of things. And then we have people like you who are putting out the research to support the things that we're doing as interventions and to continue putting out good research on the things that we can do because we have a lot of control. We're led to believe that we don't and if you're listening and you think it's hopeless, it's not. There's a lot of hope out there. So tell us about this new book. It sounds like patient stories. Tell us more about that.
Dr. Dale Bredeson 23:48
The very first person we call patient zero started back in April of 2012. A person had told her—she lives on the East Coast—”Come out to the West Coast; there's some sort of research going on out here.” I hadn't seen a patient in 20 years. We were looking at “Mountzheimers” and “Alzhclimbers” and cells dying and things like that. She asked me if I would see this person. I said: “Look, I don't see patients, but I'm happy to talk to her.” We spent several hours going through the whole idea and what this is, and she took this back to her doctor. Then she called me about three months later and said: “I cannot believe it. My memory is better than it's been in 20 years! This theory seems to be working.” I was really excited at the time. I thought, “Wow!” We've been doing this, and we've been turned down for a clinical trial back in 2011. So we then started getting more and more people.
Dr. Dale Bredeson 24:40
The best thing of all—after all of the discussion about the models and the various approaches to this—is to hear from someone that they're better and to hear how it's changed their lives. People would say [things like] “My children are so happy.” In Julie's story, she mentions that her son was crying when she first told him, “I've got Alzheimer's.” She was ApoE4/4, so she's at the highest-risk group. She was already having significant problems. She went to a neurologist and she said, “Could you at least keep me where I am?” and he said, “Good luck with that,” which was very unfortunate. He just felt, “There's nothing we can do.” Her son was crying. She got better. She just recently went to her son's wedding. So these are the best stories—hearing of how people have done better.
Dr. Dale Bredeson 25:27
As you said, we all went into medicine, [and] we all want the same thing: We want to see people get better. And this has been an area where people don't get better.
One of the things we're trying to do now is [consider]: Can we adapt the chemistry of this for all of these other diseases? We have a few of the initial people with macular degeneration. That has its own chemistry. Can we now adapt this for Lewy body [dementia] and for various other things? Although, to be fair, Lewy-body people are very much like type 3; they're the toxic ones as well, and they respond pretty well. That was the idea. I thought: “Okay, I'd love to have—a number of the people who've gone through this and done well and written these wonderful emails or phone calls—them write their stories about how it impacted their families.
Dr. Dale Bredeson 26:08
Deborah is another one—just amazing! She's a brilliant attorney who went to Harvard. She lives back East, and she wrote about how her father, a brilliant neurologist, died of Alzheimer's. Her father's mother also died of Alzheimer's. When she was getting the first symptoms, she knew it because she had seen what her father went through. She looked at her children and realized, “Oh my gosh, what's next?” She then ended up going; she was evaluated at a major medical school. She improved and they said to her [something] like: “What are you doing here? How come you're better?” She's done very well. She wrote a beautiful story about what this meant to her and to her family.
Dr. Dale Bredeson 26:47
So I thought, not only is it wonderful for people to see these heartfelt stories and to get inspiration to say, “Hey, I can do this too; we really can reduce the global burden of dementia,” but they also talk about what worked best for them. What are the things that helped them the most? What are the things that helped them the least? It really gives you some pointers as well as some inspiration.
Dr. Jill 27:07
Oh gosh, I love that and it's a team approach because if you have someone with subjective, moderate, or mild cognitive decline, you need the family members, the caretakers, and everybody involved. It sounds like you're telling that story as well.
Dr. Jill 27:24
I know we have a lot of physicians who listen to us too, Dr. Bredesen. If they're listening and they're like, “I want to learn this protocol,” tell us more about where you offer training. Where would you recommend that a doctor who wants to know more about how to treat patients go for more education?
Dr. Dale Bredeson 27:38
Yes. We just set up a new ReCODE 2.0 several months ago. There are now over 2,000 people who've gone through the training–physicians from 10 different countries and all over the USA, as you know. You can go to DrBredesen.com or you can go to ApolloHealthCo.com. The training is offered there. And it's online so it's available.
Dr. Jill 28:03
Beautiful! I love that because we really need to reach more and more. We'll be including those links wherever you're listening to this. We will include those links so you can check them out as well.
Dr. Jill 28:14
I don't want to go too deep because we go really deep with what you do for diagnosis, but just an overview. There is a big panel of labs that you recommend that I draw on these patients. We don't have to go through all of them, but let's talk maybe about classes like hormones and minerals and then also the cognoscopy. For a person who just wants a diagnosis, what basic things would you involve if they wanted to ask their doctor for those tests?
Dr. Dale Bredeson 28:38
It's a great point because you don't need to do as much for someone who's just there for prevention, assuming that they're doing well on their testing. When we talk about a cognoscopy, we include as part of that a simple online cognitive assessment because this can sneak up on people. We've had people come in for prevention and it turns out they have fairly significant MCI. We had one woman who had a MoCA [score] of 23. She was treated and went up to a perfect score of 30. She is doing very, very well.
Dr. Dale Bredeson 29:08
What we want to do is look at the very things that are the root causes, so we need to understand something about the inflammatory side and all the different subtypes that I mentioned. We'd like to look at things like hs-CRP and TGF-β1. But we'd also like to know what's driving this? Do you have a poor oral microbiome? We do look at an oral microbiome for people. We want to know what your gut status is. This was all included, by the way, in the trial that we did with Anne, Kat, and Deborah. And we want to know the basic markers for inflammation. We want to know your HOMA-IR. We want to know your metabolic status. This is such a common contributor. Even if it's not the only contributor, it's a common contributor.
Dr. Dale Bredeson 29:54
There are about 80 million Americans or so with insulin resistance, so this is a common problem. This is a problem for your brain. We used to grow brain cells. When we were in the lab, we'd grow brain cells in a dish and you always had to include insulin in the medium or else they would die. It is a very important growth factor for your brain, as are NGF, BDNF, and these other things that we're trying to improve. We'd like to know where you stand with your glycotoxicity. And then we'd like to know where you stand with your various hormones and your various nutrients.
Dr. Dale Bredeson 30:29
Many of the same risk factors for poor outcomes for COVID-19 are the same ones for Alzheimer's: Low vitamin D, hypertension, obesity, insulin resistance, vascular disease, metabolic syndrome. All of these things are important in both of these. We'd like to look at all those and that includes things like your thyroid status and free T3, not just TSH but looking very much at an IFM sort of approach. And then we'd like to know your vascular status. That's not always easy. More and more, we're finding that that is a critical one—the energetic part of this. It's the vascularity, and then it's the oxygenation. And we're looking at things like your nocturnal oxygenation. What is your SPO2? Are you dropping that? So many people are [low] without realizing it.
Dr. Dale Bredeson 31:23
I do think that some of these wearables are very helpful these days because people are now doing things like looking at their Apple Watch and saying, “Oh my gosh, I dropped to 85% oxygen saturation last night.” That's a concern. Is there something going on here? That can be a contributor. And of course, mitochondrial function. Interestingly, this is really evolving in real-time—some of the issues that I'm sure you've dealt with, for example. People have suggested methylene blue as an example of something that may be helpful [but is] not yet clear or proven. “Is this something that you like to use or not?”
Dr. Jill 32:00
I love that you mentioned this. I'm just going to take a side note really quick. One of my really good friends is the neurosurgeon for the Denver Broncos. What he sees is concussion, and how concussion contributes to early-onset dementia, those kinds of things, and even just cognitive decline in general. [After looking] over and over in the literature—he's a conventional neurosurgeon, although he knows functional medicine—he said: “Jill, there is no doubt the data supports that if you have a plain old concussion and you have no infection, no toxic load, no metabolic insufficient and no inflammation, you're probably going to be fine.” It's concussion plus [something else], which is exactly what you're talking about here. It's concussion plus Lyme disease and infection—I want to talk about that in just a second—or toxicity like mold. Mold and Lyme happened to filter to the top of our radar because they're so toxic. It doesn't mean that other viruses like Epstein-Barr, HSV, CMV, Coxsackie, or other toxins like benzene don't contribute, but you and I see a lot of this mycotoxin and a lot of Lyme.
Dr. Jill 33:00
Methylene blue happens to be really effective against an infection called Bartonella. Bartonella particularly affects the brain and nervous system, probably worse than anything else. Just yesterday, I had a consult with a 19-year-old college student who had uncontrolled rage and out-of-control anxiety. It turns out that Bartonella was the player. It was his mental status. It was profound to see how it affected his family and him, and how when he described it, it was out of proportion to what he knew himself to be, if I can say that. It was almost like the infection contributed to his response and to his irritability. It's almost like the brain was overwhelmed or the brain was on fire. We use those terms but…
Dr. Jill 33:40
And it's relative whether it's a young person with an infection or an older person with Alzheimer's; it's brain on fire in different ways. I think methylene blue and even some of these antibiotic regimens or anti-mold regimens are so critical because these [infections] are surprisingly inflammatory to the brain. I think some of the worst brain imaging that I see is related to mold and Lyme. It really does affect the brain.
Dr. Dale Bredeson 34:04
It's very interesting because, of course, it also has the effect to bypass. If you look at mitochondrial complexes, complex I is typically abnormal in Parkinson's. With Alzheimer's, it's been complex IV that's been associated. At least theoretically, if you have an inhibitor of complex I, you may be able to bypass that with methylene blue. That's theory and I think there's a lot that we don't know yet. So we want to look at all these different things and then we want to look at your mitochondrial function, as I mentioned earlier. And where do you stand with ketosis? You need to get the blood there, and you need to get the oxygen there but you'd have to have a substrate to burn. Most of these people who are developing cognitive decline are not metabolically flexible, so they're not able to go back and forth between ketosis and burning glucose. And that's critical, so getting them to optimize this is very, very helpful.
Dr. Jill 34:57
Let's talk about diet a little, because that's one of the core components of what we do with intervention and what you've taught in all of your trainings all of this time. I know you're a big fan of the ketogenic diet and I can agree. Let's talk about, really quickly for the layperson, why is that important? And are there some sub-types that may not do as well on the ketogenic diet?
Dr. Dale Bredeson 35:17
Yes, this is a really good point. I, like you, did not train as a nutritionist. When I went to medical school, there was a single course on nutrition and it was optional. I took it and I just learned one thing, which—
Dr. Jill 35:30
Or it was on TPN, the IV after surgery, right? Like, total parenteral nutrition.
Dr. Dale Bredeson 35:33
Exactly. The fact of the matter is that we're agnostic. Whatever helps the brain the most is what we want to use. What we've looked at is something we call KetoFLEX 12/3. It's a simple idea that we'd like to drive people into mild ketosis. Why do we want to do that? When you look at a PET scan, people who are ApoE4 positive are often in their late 20s, and there are already decreases in glucose utilization in the temporal and parietal regions. And that is the hallmark of all Alzheimer's; it is the signature of Alzheimer's disease. You want to be able to bridge that gap.
Dr. Dale Bredeson 36:11
As Dr. Stephen Cunnane has taught all of us over the years, you can bridge that gap by increasing ketones. Now you're able to burn, not just glucose, where you're not doing a perfect job, [but] now you add the ketones. And you get into mild ketosis—1.0 to 4.0 millimolar β-hydroxybutyrate or so. It helps you. When we see people with cognitive decline, to me, that is an energetic emergency. We already know that things aren't going well in the temporal and parietal regions with glucose utilization, so we want to do a couple of things at once. We want to start making them insulin-sensitive. We want to make them metabolically flexible and we want to get them into some ketosis so that they can bridge that gap. And they often notice, “Oh my gosh, I'm sharper when I have the ketones on board.”
Dr. Dale Bredeson 36:58
As you indicated, there's a concern because very thin people can have trouble with this. They don't have the fat to burn. We recommend: “Okay, at the beginning, just do exogenous ketones. Do some MCT oil, some coconut oil, some ketone ester, or salt, just to get it up there.” That's the quick fix. Over time, you can drive yourself into endogenous ketosis, which has some advantages over exogenous ketosis. But because there is an energy emergency at the beginning, please address that and it should help you. The very thin people are trying to get themselves into ketosis and now they have no glucose. They have no ketones and they get worse. So you have to be very, very careful.
Dr. Jill 37:44
I love that you clarify because so many people benefit but there's a small subset. I find them more likely to be atrophic—the older ones that are deficient in some of the hormones. If you have low cortisol and low estrogen loads, you are often less flexible with burning ketones as your fuel versus sugar.
Dr. Dale Bredeson 38:01
Yes. And you try to go into fasting and it makes things worse.
Dr. Jill 38:03
Also, the gut is such a big player because if you have celiac, Crohn's, or some of these things with the gut and you have malabsorption of fats, then you can eat all the fats in the world and they go right through you and you're having trouble getting them to the cells that need them. And then one last category: ApoE4/4—I'd love your opinion on this. Sometimes, because you need a high-fat diet, you need to moderate the sources of fat because if you're doing high saturated fats, you're going to drive their issues with ApoE4 and hyperlipidemia up a little. Any thoughts on those particular people, the ApoE4/4s, and fat content?
Dr. Dale Bredeson 38:39
Yes. We did some work for years on the molecular mechanisms of ApoE4. What we found very surprising is that ApoE4 enters the nucleus, interacts with 1,700 different gene promoters, and changes the programming of your cell toward a more pro-inflammatory state. It is protecting you and that's presumably why it's primordial. It's what allowed us to come down off the trees and walk around the savanna, stepping on dung and things like that. So yes, you're right: With the ApoE4/4s, you want to make several adjustments. Number one, be careful about their lipid status. You want to look at their LDL particle number. Number two, you want to give them more of the unsaturated fat, more toward the EVOOs and things like that, and away from the coconut oil. You want to be a little bit careful about that. And they do tend to absorb it. They are better absorbers than the ApoE4 negatives. And then the third thing is that you want to remember that ApoE4 itself is a pro-inflammatory gene.
Dr. Dale Bredeson 39:40
It's interesting; we're starting to see how all these things match up with the immune system. Aβ itself is part of the innate immune system. Just as people with COVID-19 die from cytokine storms, people with Alzheimer's die from cytokine drizzle because you've got this smoldering long-term problem with these cytokines, and Aβ is essentially part of that innate immune system. ApoE4 is also, as we see very clearly, a pro-inflammatory gene. One of the things that it affects with these 1,700 gene promoters is that it turns down some of the genes that normally limit the inflammatory response. Now you have less of a turning-down of your pro-inflammatory response. That's where things like resolvents can be very useful.
Dr. Jill 40:29
That makes so much sense. And like you said, there is the protective benefit. They tend not to be more of the toxic and infectious type as much. They're more inflammatory. And then the ApoE3/3s are the ones we see with the type III toxic. That's a generalization, but there's a little bit of a tendency in that direction.
Dr. Jill 40:46
In our last few minutes, what's on the horizon? Is there anything that's being studied or new in this protocol that you see as potentially something we'll look more towards in the future? Where are we headed with this research?
Dr. Dale Bredeson 41:00
This is a great point. We're now moving to a larger trial, which we'll be starting with Anne, Kat, Deborah, and probably also a few others because this is going to be a larger study. That should start next year. The second thing is to now adapt this to other things. We understand the root cause, just as you said. What about if we look at macular degeneration, Lewey body [dementia], or ALS? ALS has been one of the ones—as a neurologist—that bothered me the most. These people go downhill relatively rapidly. It's a relatively common disease, unfortunately, and it's just horrible. We need to now look at the appropriate chemistry for that and go after that. We started something called the ARC trial. We're just looking at very small numbers of people with each of these different diseases to see if we can study them very deeply. If we do a deep dive, can we see improvements?
Dr. Dale Bredeson 41:00
The third thing is something called the SARA trial, which is coming up. And this is a severe Alzheimer's reversal attempt. We'd love to get everybody at the SCI or early MCI stage. And we even had some people enter the Alzheimer's stage in this recent trial. But what about the people who have MoCA scores that are single digits? Interestingly, some of them do get better. They don't get all the way better. They get somewhat better. Sometimes, it makes a huge difference. They can dress themselves. They can speak again. But often, they don't get better.
Dr. Dale Bredeson 42:32
And I want to give a quick shout-out here to your friend, Dr. Heather Sandison, down in San Diego, who's opened Marama, which is the first assisted living facility I'm aware of that's doing the same approach and seeing people improve in their assisted living facility. But what do we do? We'd love for people never to get to Alzheimer's. But for those who are far along, what are the things we have to add? You've talked about intranasal trophic factors. You've talked about some of the peptides you've used—some beautiful approaches that you've taken. Stem cells are another one. And you've talked about this before as well. I think all of these things have potential roles. We need to understand the chemistry well enough to know: What are the critical pieces to take people who are fairly far along and bring them back as far as we can?
Dr. Jill 43:20
Yes. I love that! And this is just so encouraging. Like I said, I'm excited because I want to share it with physicians, but also with patients [who are] listening. Talk to your doctor, and get them excited about what's potential out there because they can go to Dr. Dale Bredesen's website and get more information. If you're the patient asking them, you might be the person who encourages them to get more training. We need more doctors trained.
Dr. Jill 43:43
Dr. Bredesen, I can't thank you enough for your work. You are up there in the top handful of doctors. I have such great respect for so many. You are up there in my book with what you've provided to the world, the depth of information you've added, and the information that you've given to us as clinicians down in the trenches to help us with our practice. I publicly want to say thank you so much for the work you're doing! I just love, love following that and continue to support it.
Dr. Dale Bredeson 44:13
Thank you so much. I really appreciate it. And you are doing such great work in getting so many people better! So thank you. And as you mentioned earlier, you're also seeing people younger and really preventing the problems of the future. So thank you for the great work you're doing. And I look forward to the day when all medical schools will teach modern medicine. That would be fantastic.
Dr. Jill 44:32
Yes, awesome. Well, thank you so much, Dr. Bredesen. We'll probably do part two of this at some point.
Dr. Dale Bredeson 44:38
Thank you, Dr. Jill. It's so great to talk to you.
Dr. Jill 44:40
You too. Bye-bye.
Dr. Dale Bredeson 44:41
Okay, bye-bye.
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